Flare up of rheumatoid arthritis associated with VogtKoyanagi-Harada syndrome treated with leflunomide

Dear Editor,We present a case of"Flare up of rheumatoid arthritis associated with Vogt-Koyanagi-Harada(VKH)syndrome treated with leflunomide".To our knowledge,this is the first case of uveitis and arthritis inflammation active at the same time and no treatment for this condition has been described in the literature.

Clinical efficacy of tocilizumab combined with leflunomide in the treatment of rheumatoid arthritis

Objective:To study the clinical efficacy of tocilizumab combined with leflunomide in the treatment of rheumatoid arthritis.Methods:114 patients with rheumatoid arthritis admitted from May 2015 to April 2018 were randomly divided into control group(n=57)and observation group(n=57).The control group was treated with leflunomide.On the basis of this,the observation group was treated with tocilizumab for 12 weeks.Functional indicators,erythrocyte sedimentation rate(ESR),rheumatoid factor and inflammatory factors were evaluated and adverse reactions were recorded.Results:The total treatment efficiency of the observation group(89.47%)was significantly higher than that of the control group(75.44%)(P<0.05).Morning stiffness time,joint pain score,joint swelling score,ESR,serum C-reactive protein(CRP),rheumatoid factor(RF),tumor necrosis factor(TNF-α),and interleukin-1 were observed in the observation group and the control group.The levels of IL-1),IL-6,IL-8 and other indicators were lower than those before treatment.The indexes of the observation group were significantly lower than those before treatment(P<0.05),and after treatment The morning stiffness time,joint pain score,joint swelling score,ESR,CRP,RF,TNF-α,IL-1,IL-6,IL-8 and other indicators in the observation group were significantly lower than those in the control group(P<0.05).The incidence of adverse reactions in the observation group was 14%,and the incidence of adverse reactions in the control group was 17.54%.Toltuzumab combined with leflunomide in the treatment of rheumatoid arthritis did not increase the probability of adverse reactions.Conclusion:The use of tocilizumab combined with leflunomide in the treatment of rheumatoid joints has good efficacy and safety.This may be related to a significant reduction in inflammatory factors TNF-α,IL-1,IL-6,IL-8 and the like.

Anti-inflammatory Effect of Polysaccharide from Embelia parviflora Wall.on Rheumatoid Arthritis in Rats

[Objectives]To investigate the anti-inflammatory effect of Embelia parviflora Wall.polysaccharide on rheumatoid arthritis(RA)in rats.[Methods]RA rat model was induced by type II collagen.After successful modeling,the rats were divided into model group,positive group,low,medium and high dose of E.parviflora Wall.polysaccharide groups,and normal control group.Body mass,toe volume and arthritis index were measured,and thymus index and spleen index were calculated.The levels of interleukin-1β,interleukin-6 and tumor necrosis factor-αin serum and synovial tissue of ankle joint were detected by ELISA.[Results]Compared with the normal control group,the pathological changes such as synovial hyperplasia and unclear layer were observed in the model group,the body mass was decreased(P<0.05),the toe volume,arthritis index,thymus and spleen index were increased(P<0.05),and the levels of IL-1β,IL-6 and TNF-αin serum and ankle synovial tissue were increased(P<0.05).Compared with the model group,the histopathological changes in synovium of ankle joint in the positive group and the medium and high dose groups of E.parviflora Wall.polysaccharide were significantly improved,and the body mass was increased(P<0.05).The toe volume,arthritis index,thymus index and spleen index were decreased(P<0.05).The levels of IL-Iβ,IL-6 and TNF-αin serum and synovial tissue of ankle joint were increased(P<0.05),while there was no significant difference between the low dose group of E.parviflora Wall.polysaccharide and the model group(P>0.05).[Conclusions]E.parviflora Wall.polysaccharide can reduce the body's inflammatory response and improve RA,which may be related to the inhibition of the activation of inflammatory cytokines IL-1β,IL-6 and TNF-α.

Therapeutic effect of Captopril on rheumatoid arthritis in rats

Objective:To investigate the therapeutic effect of the intervention treatment with different doses of Captopril on TNF-α contents in serum of rheumatoid arthritis(RA) rats,and to provide the theoretical proofs for clinical application of Captopril in treatments ol rheumatoid diseases.Methods:Fifty Wistar rats were randomly divided into 5 groups,namely.Group A,Group 13.Group C.Group D,Group E with 10 rats in each group.Injection of Freund’s complete adjuvant was employed to establish adjuvant-induced arthritis model in rats.Group A was model group;after model establishment,rats were treated with 20 mL normal saline as placebo(ip.).Rats in Group B were treated with 8 mg/kg cyclophosphamide(ip.).Rats in Group C.D and E were intraperitoneally injected with 30 mg/kg.100 mg/kg and 300 mg/kg Captopril respectively.Rats in each group were subjected to continuous treatment for 3 weeks,and then sacrificed.Eyeballs of rats were excised and blood was collected.TNF- α content in serum were detected using ELISA:each group rats were compared for the hind legs arthrocele.Right ankle tissues of rats were collected to prepare section,and microscopic observation of pathological changes was performed.Results:TNF- α content in serum of Group A rats was significantly higher than that of rats in other 4 groups(P【0.05).TNF- α content in serum of Group B rats was significantly lower compared with that of rats in Groups C.D and E.The highest TNF- α content in serum of rats treated with Captopril was found in Group C,followed by Groups D and E(P【0.05).Right ankle arthrocele of rats in Groups B.C.D and E in early stage showed no statistical difference compared with that of Group A rats(P】0.05).From Day 8,ankle arthrocele of rats in Groups B.C.D and E was obviously relieved compared with that of Group A rats:the anti-inflammatory effects were gradually enhanced with the extension of medication time.Treatments of Groups C.D and E showed significant activities against tardive aithrocele:the degree of ankle arthrocele in rats of these three groups was lower than that of Group A rats(P【0.01).Histological observation showed that large amount of inflammatory cells and plasmocyte infiltration was found in ankle synovial tissues of Group A rats.Relief of hyperaemia and edema of right ankle synovial tissues as well as significant decrease in synoviocyte layer hyperplasia,intra—articular inflammatory cells infiltration and cartilage articularis damage degree etc.were observed in Groups B.C.D and E.Conclusions:Intervention treatment with Captopril can effectively reduce the TNF- α content in serum of rheumatoid arthritis rats and inhibit the generation of inflammatory factors,so as to achieve the therapeutic effect.

Leflunomide,a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase Ⅱ clinical trial

Objective To evaluate the efficacy and safety of leflunomide in comparison with methotrexate (MTX) on patients with rheumatoid arthritis (RA) in China.Methods Five hundred and sixty-six patients with active rheumatoid arthritis were randomly assigned to receive leflunomide at 20 mg once daily or MTX at 15 mg once weekly in a controlled trial. Five hundred and four patients completed the 12-week treatment and some patients continued the treatment for 24 weeks. Results Both leflunomide and MTX could improve the symptoms,signs,and joint function,but there were no changes in X-ray observations of patients with rheumatoid arthritis. In the leflunomide group,the overall rates of effectiveness at 12 weeks and 24 weeks were 86.94% and 92.31% respectively; the rates of remarkable improvement were 64.95% and 79.81% respectively. In the MTX group,the overall rates of effectiveness at 12 weeks and 24 weeks were 84.04% and 83.15% respectively; the rates of remarkable improvement were 56.81% and 75.28% respectively. According to intent-to-treat analysis,the ACR 20% response rates at 12 weeks and 24 weeks in the leflunomide group were 62.54% and 67.18% respectively,compared with 60.08% and 61.32% respectively in MTX group. No statistical differences were shown in the efficacy between the two groups ( P >0.05). The adverse events in the leflunomide group were gastrointestinal symptoms,skin rash,alopecia,nervous system symptoms,decreased leukocyte count,and elevation of alanine aminotransferase (ALT). Most of these side effects were mild and transient. The incidence of adverse events in the leflunomide group was 16.84%,significantly lower than that in MTX group (28.17%,P =0.002).Conclusions Leflunomide is effective in the treatment of RA with less adverse events than MTX. Its efficacy is similar to MTX,but the incidence of adverse events and the rate of withdrawal due to adverse events were lower in the leflunomide group than in MTX group.

Is non-biological treatment of rheumatoid arthritis as good as biologics?

The management of rheumatoid arthritis(RA) in the past three decades has undergone a paradigm shift from symptomatic relief to a "treat-to-target" approach. This has been possible through use of various conventional and biologic disease modifying anti-rheumatic drugs(DMARDs) which target disease pathogenesis at a molecular level. Cost and infection risk preclude regular use of biologics in resource-constrained settings. In therecent years, evidence has emerged that combination therapy with conventional DMARDs is not inferior to biologics in the management of RA and is a feasible cost-effective option.

Arava Treatment,between Beneficial Action on Joint Inflammation and Side Effects on Liver,Myocardium and Kidney in Experimental Murine Arthritis

The purpose of the experiment was the follow-up in time of the course of joint inflammation phenomena in laboratory animals (white female adult Wistar rats) by determining particular biological, hematological, radiological, osteodensitometric, immunological and anatomic-pathological parameters and by assessing the effects of Leflunomide (Arava) on the course of the disease. ARAVA&reg;(Leflunomide) is a pyrimidine synthesis inhibitor. The experimental study was conducted for 8 weeks. We have also assessed the side effects of the therapy on their liver, myocardium and kidney. Leflunomide therapy improved the course of the clinical and paraclinical parameters, but it did not cure the condition. The positive results in the joints were accompanied by many histological alterations. The experiment revealed the toxic visceral effects of Leflunomide on the liver, heart and kidney.

Effect of Artemisia annua Extract on Treating Active Rheumatoid Arthritis:A Randomized Controlled Trial

Objective：To investigate the effect and safety of the complementary use of the extract of Artemisia annua L.（EAA） on treating active rheumatoid arthritis（RA）. Methods：A randomized controlled clinical trial was performed. All the 159 participates with active RA were randomly assigned to the control group（80 cases） and EAA group（79 cases） using concealed random allocation method. In the control group, patients were medicated with leflunomide and methotrexate for 48 weeks; and patients in the EAA group were administrated with leflunomide, methotrexate plus EAA（30 g/d）. At the time points of 0, 12, 24 and 48 weeks, the clinical outcome measures, including objective pain score, tenderness score, number of painful joints, number of swollen joints, health assessment questionnaire（HAQ） score for quality of life, levels of serum rheumatoid factor（RF）, anti-cyclic citrullinated protein antibodies（CCP-Ab）, erythrocyte sedimentation rate（ESR）, C reactive protein（CRP）, visual analogue score for pain（VAS）, and the overall efficacy were detected and recorded. Results：The objective pain score, number of painful joints and ESR at 12 weeks, tenderness score and HAQ at 24 weeks, and the tenderness score, number of painfull joints, number of swollen joints, HAQ, CRP, RF and CCP-Ab at 48 weeks were significantly improved in the EAA group compared with the control group（P〈0.01 or P〈0.05）. At 24 and 48 weeks, the overall efficacy of the EAA group was significantly higher than the control group（P〈0.01）. There were significantly higher withdrawal rate of corticosteroids within 12 weeks post-treatment and lower incidence rate of adverse effects in the EAA group compared with the control group（P〈0.01 or P〈0.05）. Conclusion：EAA plus methotrexate and leflunomide were more effective and safer than the routine use of methotrexate and leflunomide in the treatment of active RA.

Nanoenzyme engineered neutrophil-derived exosomes attenuate joint injury in advanced rheumatoid arthritis via regulating inflammatory environment

Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint.Inspired by neutrophil chemotaxis for inflammatory region,we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles(uPB-Exo)via click chemistry,inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties.uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes,subsequently neutralizing pro-inflammatory factors,scavenging reactive oxygen species,and alleviating inflammatory stress.In addition,uPB-Exo effectively targeted to inflammatory synovitis,penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system,leading to precise diagnosis of RA in vivo with high sensitivity and specificity.Particularly,uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation,thereby significantly ameliorating joint damage.Therefore,nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.

广义估计方程评估调督通脉针灸法治疗不同年龄临床前类风湿关节炎的效果

背景:针灸在类风湿关节炎中的治疗效果尚存在争议。因此,该研究旨在通过广义估计方程评估调督通脉针灸法治疗不同年龄临床前类风湿关节炎患者的效果,为针灸在类风湿关节炎中的应用提供依据。目的:基于广义估计方程探讨调督通脉针灸法对不同年龄临床前类风湿关节炎患者的影响。方法:选取2023年1-9月收治的123例临床前类风湿关节炎患者为研究对象,根据治疗方法不同分为研究组(n=64)和对照组(n=59),研究组给予调督通脉针灸治疗,对照组给予乙酰氨基酚片治疗。采用倾向性评分匹配法调整基线均衡性,比较两组患者临床疗效和治疗前后细胞因子水平,建立广义估计方程模型评估调督通脉针灸法治疗不同年龄临床前类风湿关节炎患者的效果。结果与结论:(1)治疗0 d,研究组和对照组在关节疼痛、C-反应蛋白方面存在显著差异(P<0.05);治疗4周,两组患者在目测类比评分、关节疼痛、C-反应蛋白、红细胞沉降率方面存在显著差异(P<0.05);治疗8周,两组患者在目测类比评分、C-反应蛋白、红细胞沉降率方面存在显著差异(P<0.05);治疗12周,两组患者在目测类比评分、C-反应蛋白、红细胞沉降率方面存在显著差异(P<0.05)。(2)研究组治疗后总有效率为93.75%,对照组为79.17%,研究组患者临床疗效显著优于对照组(P<0.05)。(3)研究组治疗后在白细胞介素6、干扰素γ、巨噬细胞迁移抑制因子、类风湿因子IgA、类风湿因子IgM、基质金属蛋白酶3、基质金属蛋白酶9、抗环状瓜氨酸抗体方面与治疗前相比差异显著(P<0.05);对照组治疗后在白细胞介素6、干扰素γ、类风湿因子IgA、类风湿因子IgM、基质金属蛋白酶3、基质金属蛋白酶9、抗环状瓜氨酸抗体方面与治疗前相比差异显著(P<0.05);研究组治疗后在白细胞介素6、干扰素γ、巨噬细胞迁移抑制因子、类风湿因子IgA、类风湿因子IgM、基质金属蛋白酶3、抗环状瓜氨酸抗体方面与对照组治疗后相比差异显著(P<0.05)。(4)治疗12周,研究组各年龄段患者综合疗效优于对照组(P<0.05);治疗8周,研究组23-35岁、36-50岁、51-60岁患者的综合疗效优于对照组(P<0.05),两组18-22岁患者综合疗效相当;治疗4周,研究组36-50岁、51-60岁患者综合疗效优于对照组(P<0.05),两组18-22岁、23-35岁患者综合疗效相当。结果表明,调督通脉针灸法治疗36-50岁、51-60岁临床前类风湿关节炎患者具有一定优势。

依那西普联合来氟米特治疗老年类风湿关节炎的疗效及对骨代谢指标、炎症因子及红细胞沉降率的影响

目的观察依那西普联合来氟米特治疗老年类风湿关节炎的疗效及其对患者骨代谢指标、炎症因子及红细胞沉降率的影响。方法前瞻性选择2019年12月至2020年12月河北省沧州中西医结合医院收治的94例老年类风湿关节炎患者为研究对象,按照随机数字表法将其分为观察组和对照组,每组各47例。对照组给予来氟米特、扶他林口服治疗,来氟米特1次/d,2片/次,扶他林3次/d,1片/次;观察组在对照组基础上给予依那西普皮下注射,25 mg/次,2次/周,两组均治疗12周。比较两组临床疗效,治疗前、治疗12周后疾病活动指标[晨僵时间、关节触痛个数、关节肿胀个数、视觉模拟评分法(VAS)评分];检测骨代谢指标{血清25羟维生素D[25(OH)D]、Ⅰ型胶原羧基端肽交联(β-CTX)、骨钙素水平、炎症因子[肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)]及红细胞沉降率;记录两组不良反应发生情况。结果两组治疗总有效率分别为80.85%、65.96%,比较差异无统计学意义(P>0.05)。治疗12周后,观察组的晨僵时间为(56.92±13.78)min,短于对照组[(72.06±22.64)min],观察组的关节触痛个数、关节肿胀个数分别为(6.39±2.07)、(1.95±0.47)个,少于对照组[(11.26±3.19)、(2.14±0.51)个],观察组的VAS评分为(2.74±0.71)分,低于对照组[(4.26±0.95)分],差异均有统计学意义(P<0.05)。治疗12周后,两组血清25(OH)D、骨钙素水平均较治疗前升高,血清β-CTX水平均较治疗前降低,观察组血清25(OH)D、骨钙素水平分别为(19.06±4.26)、(28.53±5.14)ng/mL,均高于对照组[(16.17±4.41)、(25.49±6.53)ng/mL],血清β-CTX水平为(0.42±0.14)ng/mL,低于对照组[(0.64±0.22)ng/mL],差异均有统计学意义(P<0.05)。治疗12周后,两组血清TNF-α、hs-CRP水平及红细胞沉降率均较治疗前降低,观察组血清TNF-α、hs-CRP水平及红细胞沉降率分别为(4.92±1.18)μg/L、(6.49±2.18)mg/L、(41.92±13.96)mm/h,均低于对照组[(7.44±1.54)μg/L、(8.63±2.56)mg/L、(61.77±19.82)mm/h],差异均有统计学意义(P<0.05)。两组不良反应发生率分别为14.89%、8.51%,比较差异无统计学意义(P>0.05)。结论依那西普联合来氟米特治疗老年类风湿关节炎有利于减轻晨僵、关节触痛、关节肿胀等症状,可改善骨代谢指标、减轻炎症反应、下调红细胞沉降率,安全性较好,具有推广价值。

烧山火针刺法联合甲氨蝶呤治疗类风湿关节炎活动期的效果及其对患者炎症因子和免疫功能的影响

目的 观察烧山火针刺法联合甲氨蝶呤治疗类风湿关节炎(RA)活动期的效果,并探讨其抗炎和调节免疫作用机制。方法 选取2020年2月至2022年10月郑州市第一人民医院收治的60例RA活动期患者纳入研究,按照随机数表法分为常规组和联合组各30例。常规组患者给予甲氨蝶呤治疗,联合组患者给予烧山火针刺法联合甲氨蝶呤治疗,均治疗两周。于治疗两周后比较两组患者的治疗效果,以及治疗前后的中医证候评分、28个关节疾病活动(DAS28)评分、疼痛(VAS)评分、炎性指标[血沉(ESR)、C反应蛋白(CRP)、肿瘤坏死因子-α (TNF-α)、类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体]、免疫指标(Treg细胞、Th17细胞、Treg/Th17细胞),同时比较两组患者治疗期间的不良反应发生情况。结果 联合组患者的治疗总有效率为93.33%,明显高于常规组的73.33%,差异有统计学意义(P<0.05);联合组患者治疗两周后的中医证候关节肿胀、冷痛、压痛、晨僵、屈伸不利评分分别为(0.72±0.18)分、(0.70±0.20)分、(0.81±0.22)分、(0.68±0.15)分、(0.77±0.19)分,明显低于常规组的(1.03±0.24)分、(0.96±0.23)分、(1.14±0.26)分、(0.91±0.21)分、(1.09±0.23)分,差异均有统计学意义(P<0.05);联合组患者治疗两周后的DAS28、VAS评分分别为(2.18±0.33)分、(2.46±0.22)分,明显低于常规组的(3.26±0.47)分、(2.89±0.27)分,差异均有统计学意义(P<0.05);联合组患者治疗两周后的ESR、抗CCP抗体、RF、CRP、TNF-α水平分别为(16.23±2.29) mm/h、(172.30±30.14) IU/mL、(130.85±15.42) IU/mL、(10.20±1.68) mg/L、(18.95±4.38) pg/mL,明显低于常规组的(21.84±3.41) mm/h、(205.68±36.77) IU/mL、(157.62±24.10) IU/mL、(13.65±2.06) mg/L、(24.51±6.02) pg/mL,差异均有统计学意义(P<0.05);联合组患者治疗两周的外周血Treg细胞百分比、Treg/Th17比值分别为(2.61±0.35)%、2.44±0.37,明显高于常规组的(2.17±0.28)%、1.68±0.32,Th17细胞百分比为(1.07±0.18)%,明显低于常规组的(1.29±0.22)%,差异均有统计学意义(P<0.05);两组患者治疗期间的不良反应发生率差异无统计学意义(P>0.05)。结论 烧山火针刺法联合甲氨蝶呤治疗RA活动期能明显减轻患者的临床症状,降低炎症反应,调节免疫功能,临床应用疗效显著,且安全性良好。

补肾蠲痹汤联合甲氨蝶呤治疗老年类风湿关节炎的临床效果

目的研究补肾蠲痹汤与甲氨蝶呤联合使用对老年类风湿关节炎的治疗效果。方法回顾性选取2019年10月—2022年10月汉川市人民医院收治的118例老年类风湿关节炎患者的临床资料,以不同治疗方式分为两组,对照组(58例)给予口服甲氨蝶呤片治疗,观察组(60例)采用口服甲氨蝶呤片+补肾蠲痹汤治疗。比较两组晨僵时间及中医证候积分、视觉模拟评分法、类风湿性关节炎28个关节疾病活动评分、健康评估问卷评分、炎症因子水平、不良反应、治疗有效率。结果治疗后,观察组晨僵时间短于对照组,中医证候积分、视觉模拟评分法评分、类风湿性关节炎28个关节疾病活动评分及健康评估问卷评分低于对照组,差异有统计学意义(P均<0.05)。治疗后,观察组红细胞沉降率、类风湿因子、C反应蛋白、肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6水平低于对照组,差异有统计学意义(P均<0.05)。治疗后,两组不良反应发生率比较,差异无统计学意义(P>0.05)。观察组治疗有效率为95.00%(57/60),高于对照组的82.76%(48/58),差异有统计学意义(χ^(2)=4.505,P<0.05)。结论与单独使用甲氨蝶呤相比,补肾蠲痹汤与甲氨蝶呤联合使用在改善老年类风湿关节炎的临床症状方面具有更显著的优势,还能有效降低炎症因子水平,同时不增加不良反应的发生风险。

散寒除湿汤联合西药治疗老年类风湿关节炎对患者DAS28、HAQ评分的影响

目的观察散寒除湿汤联合西药治疗老年类风湿关节炎(elderly-onset rheumatoid arthritis,EORA)对患者类风湿关节炎疾病活动(disease activity score for rheumatoid arthritis 28,DAS28)、健康评估问卷(health assessment questionnaire,HAQ)评分的影响。方法选取2020年6月—2022年8月濮阳市安阳地区医院收治的98例EORA患者,随机分为对照组与研究组各49例。对照组给予常规西药治疗,研究组给予散寒除湿汤联合西药治疗,均治疗3个月。比较两组患者的临床疗效、晨僵时间、关节肿胀数(swollen joint count,SJC)、关节压痛数(tenderness joint count,TJC)、DAS28评分、HAQ评分、红细胞沉降率(erythrocyte sedimentation rate,ESR)水平、类风湿因子(rheumatoid factor,RF)水平、C-反应蛋白(C-reactive protein,CRP)水平以及不良反应发生情况。结果治疗后,研究组患者的总有效率为93.88%(46/49),高于对照组的75.51%(37/49)(P<0.05);研究组患者的晨僵时间、SJC及TJC均低于对照组(P<0.05);研究组患者的DAS28评分及HAQ评分均低于对照组(P<0.05);研究组患者的ESR、RF及CRP水平均低于对照组(P<0.05);两组患者的不良反应发生率比较差异无统计学意义(P>0.05),且均未见有明显严重不良反应发生。结论散寒除湿汤联合西药治疗EORA,可提升疗效,有效缓解患者症状,改善机体炎性反应与健康状况,安全性好。

不同剂量雷公藤总苷联合西药治疗类风湿性关节炎疗效比较

目的探讨不同剂量雷公藤总苷联合美洛昔康片治疗类风湿性关节炎的疗效及安全性。方法选择80例类风湿性关节炎患者,按照随机数表法分为大剂量组与小剂量组,各40例。2组均给予美洛昔康片治疗,大剂量组给予每次20 mg雷公藤总苷,小剂量组给予每次10 mg雷公藤总苷,2组均治疗2个月。比较2组临床疗效;治疗前、治疗2个月后,比较2组关节功能障碍分级、晨僵时间、关节视觉模拟疼痛评分(VAS)、双手平均握力、关节压痛数、关节肿胀数及白细胞介素-6(IL-6)、红细胞沉降率(ESR)、类风湿因子(RF)、C-反应蛋白(CRP)水平;观察2组不良反应发生情况。结果大剂量组临床疗效优于小剂量组(P<0.05)。治疗后,大剂量组关节功能障碍分级I级人数明显多于小剂量组(P<0.05),Ⅲ级人数明显少于小剂量组(P<0.05);大剂量组晨僵时间、VAS评分、关节压痛数、关节肿胀数水平、IL-6、ESR、RF、CRP水平低于小剂量组(P<0.05),双手平均握力水平高于小剂量组(P<0.05)。2组不良反应发生情况比较,大剂量组发生不良反应略多于小剂量组,差异无统计学意义(P>0.05)。结论大剂量雷公藤总苷联合美洛昔康片的疗效优于小剂量雷公藤联合美洛昔康片,能够有效减轻患者临床症状,降低炎症因子水平,但有可能增加不良反应发生风险,临床需要根据实际情况调整雷公藤总苷给药量。

基于生物信息学方法筛选甲氨蝶呤治疗类风湿关节炎疗效的生物标志物

目的通过生物信息学方法研究外周血白细胞中影响甲氨蝶呤治疗类风湿关节炎疗效的关键调控因子,为类风湿关节炎精准治疗提供参考。方法应用GEO公共数据集,根据DAS28和ΔDAS28变化将患者分为响应组与非响应组,使用R语言寻找两组的DEGs,构建蛋白-蛋白互作网络筛选关键基因,同时对差异基因进行功能和通路富集分析,构建Lasso回归模型预测甲氨蝶呤疗效。结果响应组与非响应组的基因表达轮廓存在明显差异,共发现71个DEGs,网络度值分析筛选出16个关键基因;差异基因功能主要体现在抗原提成、细胞杀伤、自然杀伤细胞介导的细胞毒作用、T细胞受体信号通路等。应用CCL5、EOMES、LAG3、KLRG1、KLRC2基因构建Lasso回归模型,模型在训练集的AUC值为0.83,在验证集的AUC值为0.67。结论本研究发现了预测甲氨蝶呤治疗效果的关键基因,并阐述了其潜在耐药机制,为类风湿关节炎治疗方案的制订提供依据。

甘草对雷公藤治疗类风湿关节炎减毒增效的研究进展

雷公藤是中医治疗风湿性疾病常用的中草药,对以类风湿关节炎(rheumatoid arthritis,RA)为主的风湿性疾病起到良好的治疗作用,但由于其存在的不良反应使得该药的使用受到限制。甘草是中医传统的解毒药物,以甘草对雷公藤治疗RA为例,通过对近些年的文献进行综述,发现甘草可以通过影响机体的应答以及影响药物在体内的代谢过程对雷公藤治疗RA起到减毒增效的作用。既往尚未有综述对这方面的内容进行讨论,希望通过综述,能为安全使用雷公藤及其相关制剂提供技术参考,为RA的发病机制研究提供理论依据,以及对复方的研究和新药的研发提供思路。

基于血清生化指标及DAS28、HAQ评分变化探究桂枝芍药知母汤联合西药在老年类风湿关节炎急性期治疗中的应用效果

目的:探究桂枝芍药知母汤联合西药治疗对风寒湿痹型老年类风湿关节炎(RA)急性期患者血清生化指标及DAS28、HAQ评分的影响。方法:选取风寒湿痹型老年RA急性期患者86例为研究对象,采用抽签法随机分为观察组(桂枝芍药知母汤联合来氟米特)及对照组(来氟米特)各43例,比较治疗前及治疗3个月后两组患者中医证候积分、血清生化指标[血沉(ESR)、C-反应蛋白(CRP)、类风湿因子(RF)水平、抗环瓜氨酸肽抗体(CCP)]、免疫功能指标[外周血CD4^(+)T淋巴细胞水平(CD4^(+))、CD8^(+)T淋巴细胞(CD8^(+))水平及其比值(CD4^(+)/CD8^(+))]、关节功能恢复情况[28个关节病情活动指数(DAS28)、健康评价问卷得分(HAQ)],观察并记录两组患者治疗过程中不良反应情况。结果:与治疗前相比,观察组患者治疗3个月后血清生化指标、免疫功能指标(CD4^(+)、CD4^(+)/CD8^(+))、关节功能恢复情况均呈下降趋势,且观察组明显低于同期对照组(P<0.05);观察组CD8^(+)水平明显高于同期对照组(P<0.05);两组患者不良反应发生比较均无统计学差异(P>0.05)。结论:桂枝芍药知母汤联合西药治疗可有效平衡患者免疫功能,降低其机体炎症水平,促进关节功能恢复,具有较好临床疗效。

托法替布治疗类风湿关节炎继发干燥综合征临床疗效

目的探讨分析托法替布对类风湿关节炎继发干燥综合征患者的治疗效果。方法选取2021年5月—2023年2月泰州市第二人民医院收治的72例类风湿关节炎继发干燥综合征患者为研究对象,按照信封随机法分为两组,参照组(36例)接受单纯甲氨蝶呤治疗,研究组(36例)联合托法替布治疗,比较两组的治疗效果。结果治疗后,研究组肿胀关节个数(3.8±1.0)个、压痛关节个数(6.3±2.0)个均少于参照组的(4.7±1.6)、(8.6±2.1)个,差异有统计学意义(t=2.862、4.759,P均<0.05);研究组类风湿关节炎治疗有效率为97.22%,高于参照组的77.78%,差异有统计学意义(χ^(2)=6.222,P=0.013);研究组干燥综合征治疗有效率为(97.22%)高于参照组(80.56%),差异有统计学意义(χ^(2)=5.062,P=0.024)。结论对类风湿关节炎继发干燥综合征患者采用托法替布进行治疗,能够取得极为确切的疗效,缓解患者的病情,减轻患者的临床不适症状,改善其生活质量。同时,能够调节患者的机体状态,切实减轻患者的关节压痛程度,使患者可以恢复正常的工作与生活。

小剂量来氟米特配合甲氨蝶呤治疗老年类风湿关节炎患者的效果

目的探讨小剂量来氟米特配合甲氨蝶呤治疗老年首发类风湿关节炎(rheumatoid arthritis,RA)患者的效果。方法选取2020年2月至2023年2月西安市第五医院收治的120例老年首发RA患者进行随机对照试验。采用随机数字表法将其分为配合组及参考组,各60例。配合组男37例,女23例,年龄(70.22±5.29)岁,体质量指数(body mass index,BMI)(22.87±1.55)kg/m^(2),病程(4.76±0.85)年。参考组男38例,女22例,年龄(70.31±5.34)岁,BMI(22.94±1.58)kg/m^(2),病程(4.82±0.87)年。参考组采用甲氨蝶呤治疗,配合组则于参考组的基础上采用小剂量来氟米特治疗。两组均治疗90 d。对比两组临床疗效,临床症状改善情况,治疗前后骨代谢指标水平和血清壳多糖酶3样蛋白1(chitinase 3-like protein1,CHI3L1)、可溶性基质裂解素2(soluble suppression of tumorigenicity 2,sST2)、白细胞介素-32(interleukin-32,IL-32)水平,不良反应。采用χ^(2)检验和t检验。结果配合组总有效率高于参考组[96.67%(58/60)比83.33%(50/60)](χ^(2)=5.926,P=0.015)。配合组关节压痛数目、关节肿胀数目分别为(5.23±1.05)个、(4.18±0.66)个,均少于参考组的(7.45±1.36)个、(6.39±0.82)个,晨僵时长为(34.58±4.68)min,短于参考组的(50.40±8.21)min,双手握力为(14.03±2.55)kPa,高于参考组的(11.28±2.09)kPa(t=10.008、16.263、12.967、6.461,均P<0.001)。治疗后,配合组骨钙素(bone gla protein,BGP)、骨保护素(osteoprotectin,OPG)及总Ⅰ型胶原氨基端延长肽(total type I collagen amino terminal extension peptide,T-PⅠNP)水平分别为(27.48±5.02)ng/L、(5.02±0.74)ng/L、(43.17±8.59)μg/L,均高于参考组的(24.16±4.19)ng/L、(4.45±0.66)ng/L、(36.92±7.33)μg/L(t=3.933、4.453、4.287,均P<0.001)。治疗后,配合组血清CHI3L1、sST2、IL-32水平分别为(50.82±6.12)μg/L、(28.45±4.11)μg/L、(14.32±2.01)ng/L,均低于参考组的(78.45±8.39)μg/L、(33.05±5.24)μg/L、(16.85±2.77)ng/L(t=20.609、5.350、5.726,均P<0.001)。两组不良反应发生率对比,差异无统计学意义(P>0.05)。结论小剂量来氟米特配合甲氨蝶呤应用于老年首发RA患者中的效果较佳,可改善患者骨代谢指标及血清CHI3L1、sST2、IL-32水平。